How to sustain high patient compliance in medical device trials

A comparison between pharma trials and medical device clinical trials

Truth or fiction - medical device trials are simpler than pharma

The differences between medical device trials and drug efficacy studies are similar to the differences between starting a law firm and starting a business training runners – while both are businesses in a basic sense, they each have specific criteria to adhere to regarding government regulation of standards and practices, and varying endpoints to determine whether the customer/client is satisfied and a task is finally complete.

There is also a vast difference in numbers and uses. More than 500,000 different types of medical devices are produced globally – compared to 20,000 medicinal products – each in service of vastly diverse indications.

For the law firm – regulatory compliance impinges on the lawyer and for running – compliance hinges almost totally on the runner.

But the analogy is not arbitrary.   Pharma trials are like law firms – where protocol compliance is primarily the responsibility of the principal investigator.     Trainers are like medical device trials – where protocol compliance is primarily the personal responsibility of the runner (the patient).

Before we examine and reveal whether or not clinical monitoring of medical device trials is easier than clinical trial monitoring for pharmaceutical trials, it is better to understand that first of all they are significantly different from one another.

Simpler, or just different?

During pharmaceutical testing, extensive clinical trials are necessary to evaluate the efficacy and safety of each and every drug, every single time pharma develops a drug in hopes of bringing it to market. With regards to medical devices, some do not even require a trial whatsoever. For example, a simple bandage is indeed considered a medical device, and subject to regulatory body regulation. Yet, a bandage for protecting a healing, minor laceration will not require a clinical trial during design and development.

When we refer to a “medical device”, it is a blanket term and can refer to everything from gauze or scalpel to a prosthetic limb or stent. For devices that pose a risk to patient safety, a trial must be conducted. That being said, while every drug needs to be tested through Phase I to Phase III, and monitored after it is brought to market during Phase IV, medical devices that pose minor risk to patient safety do not require the degree of testing that higher risk devices do.

While many medical devices are exempt from clinical trials pre-marketing, interventional medical devices for chronic diseases like migraine and chronic constipation require a series of clinical trials even for predicate devices.     Since chronic disease involve home use medical devices – the issue of patient compliance becomes acute and real-time clinical becomes a critical success factor for the medical device clinical trial. 

Given unique indications and interventions, for high-risk medical devices, such as powered units like pacemakers or radiation generators like x-rays, the clinical trials required before bringing them to market can rival pharmaceutical testing in scope and complexity. Both industries require regulatory compliance, for example with 21 CFR Part 11 for electronic record documentation and storage.

Again, it is like comparing a running trainer to a lawyer – the trainer needs to ensure that she keeps her runners on track with a safe but continuously-improving running schedule (volume and speed), and the lawyer needs to sustain a practice that meets regulatory and ethical standards. Even though each vocation presents their unique challenges, both the trainer and the lawyer need to file their taxes at the end of the year or answer to the IRS.

That being said, when all is accounted for, the trainer probably has a more challenging compliance situation than the lawyer. Let us examine this question by  comparing medical device clinical trials to drug trials.

Randomization vs fixed group

One key difference during the clinical trial of a drug or medical device may be the randomization of study subjects. Pharma demands that patients be randomized when monitoring and evaluating a drug’s efficacy and side-effects, and drugs are wildly less predictable than a device.

Placebo monitoring

When developing and testing a device, regardless of whether it is an MRI or a syringe, there is no placebo to test it against – the device is either performing as expected or needs adjustments/redesign. Drugs are metabolized by the body, whereas devices simply demonstrate their functionality or not.

In this case, medical device trials are measurably simpler than their pharmaceutical counterparts, requiring less study subjects and less long-term monitoring before making it to market.

Number of study sites and subjects

Pharma clinical studies, especially Phase II and beyond, involve a vastly greater number of study subjects (Phase III is typically in the thousands) across any number of study sites, often in multiple countries. Medical device clinical trials testing for efficacy may involve smaller numbers of sites and subjects – on the order of 10-20 sites and less than 1000 subjects. However, the somewhat lower number of subjects is more than offset by generally large numbers of variables that are collected per subject – typically as much as a 1000 variables not including repeat visits.

Blinding and clinical monitoring

Drug trials, in an effort to mitigate bias toward efficacy, are conducted using blind controls – where the patient knows not whether they are being administered an active drug or placebo, or double blind – where neither clinician nor subject are aware of placebo or drug during testing.

Medical device studies’ requirements for blinding  and clinical monitoring in safety and efficacy studies can be quite complex with requirements for CRF and user role level blinding, in order to prevent investigators from being biased during recruitment and in order to prevent blinded evaluators such as histologists from being influenced by site findings. In this respect, medical device trials may actually have a higher level of complexity for clinical trial monitoring due to blinding requirements. When patients are blinded, ensuring patient compliance becomes a difficult technical challenge for EDC systems and generally requires a separate CTMS and ePRO system which then cascades into HIPAA and GDPR privacy requirements. 

CRO staff training

With pharmaceutical clinical trials, sponsors need to ensure that staff are trained in the data capture system planned for the study, whether it is paper-based or EDC. Either way, except for brand new clinicians, monitors, managers, etc. it is far more likely than not that the CRO staff have experience with paper systems.

If switching to EDC from paper, the bulk of the data capture and monitoring logic stays the same, and minimal onboarding (2-4 weeks) is required. After being initially trained, CROs have an understanding of the system, and the knowledge can be applied to future studies without a hitch.

However, this is not the case for connected medical device studies, which are much more complex concerning CRO training. With drugs, pharmacologists do the legwork with regards to design – CROs simply run the trial, collect data, and monitor results. It is repetitive, study after study.

Medical devices are new technology each time they are studied, and the complexity and/or safety risks of some Class III devices can be staggering. A CRO with ample drug trial experience cannot apply their knowledge to a device study without first training clinicians, monitors, managers, and support staff with proper device operation. Especially for CROs not yet experienced with a device of similar nature, the device conduct training can be exhaustive and intensive, taking far more time and resources to amply familiarize staff with the device being tested.

So, truth or fiction?

The answer is – both. In many regards, device trials are simpler to conduct, but they present their own unique challenges for patient compliance that pharma often ignores – since the CRO is designating responsibility for patient compliance to the sites.

While both types of trials need to be equally compliant with regulatory guidelines, medical device trials pose sizable challenges due to patient compliance issues – whether compliance of patient-reported outcomes or whether compliance of patients to the treatment protocol.

Is social networking a threat or an opportunity for patient compliance?

Climbing the mountain of compliance

As CEO or VP Clinical and regulatory, do you see social networking as an opportunity or as a threat for your medical device clinical trials ?

From a cyber security and privacy perspective, an immediate reaction might be to focus on threats to privacy and intellectual property and answer no to the above question, but social networking is so part of our lives today, it is impossible to ignore. Your patients and your site coordinators are on Instagram whether you like it or not.

The challenge of privacy, GDPR and HIPAA Security Rule compliance for medical device clinical trials is no longer a problem to be solved by lawyers. The value and advantage of ePRO, connected medical devices, eSource and cloud EDC make these technologies a must for medical device clinical trials.

While privacy regulation are obvious constraints, there is a tremendous opportunity for social media and private social networking technologies to accelerate the patient recruitment process, support patient engagement and enrich the medical device clinical operations team with better information regarding patient compliance in medical device clinical trials.

For home-use and chronic disease medical device – the objectives of high levels of patient compliance are top priority for every medical device CEO.

The value of high levels of patient compliance to the clinical protocol are clear to medical device CEOs who embrace online  and modern cloud technologies.  But the importance of patient compliance in clinical trials appears less clear for big pharma who are reluctant adopters of private social networking and social media in general..

… So why do big pharma have a problem with social?

Big pharma are online with a wealth of information as a public service. Medical devices, esthetics and food supplements have run their business online for years. 

While big pharmaceutical companies are not major social networking players – they do know how a lot about online marketing.  Let’s talk about work that Sanofi-Aventis has been doing online since 2009.

Sanofi Aventis portfolio includes research and development and manufacturing of new medications. They cover 7 major therapeutically areas: cardio, thrombosis, oncology, diabetes, CNS, internal medicine and vaccines. The site has loads of information concerning the company such as: Press releases, material targeted to draw the attention of possible investors, access to the Research and development section where you can learn about the newest medications as well as their future plans and their clinical trails plus guests can apply for the different clinical research experiments.

On the other hand – it’s easy to try out social media and see if you get traction. The energy barrier is so low and the leverage on Youtube is so high, it’s an irresistible force pushing on a very heavy object like this:

Beautiful landscape
This is an immovable object.

Behind the science

Sanofi Aventis and AstraZeneca Launch YouTube Sites – Social media has been a buzzword in the pharmaceutical industry for the past few years (see ePharma Summit), but few companies have crossed the line into the world of social networking or conducting two-way conversations with patients online.

Feb 18, 2009 

The Sanofi channel is part of its integrated GoInsulin campaign, an unbranded health education program designed to give people more information about diabetes and serve as a launching pad to the Sanofi homepage. It features an array of patient videos and a link to an off-site, online game that separates the myths about insulin from reality. The channel has no branded drug material, but lists the company’s name below the top banner.

Although social media like Twitter is dominantly about personal opinions and experiences, social software such as blogs, micro-blogs and file sharing have important collaborative applications.

For example – like how to integrate all the information and care of a patient with multiple issues and care-givers (a typical MSA patient will have a GP, neurologist, speech therapist, physiotherapist, nutritionist and primary care giver at home who is usually the  husband or wife of the patient with problems of their own. Speaking before a conference of the Case Management Society of America in October 2007, Tim Rothwell from Sanofi Aventis discussed their commitment to help resolve problems of collaborative care

The issues and challenges of poor transitions of care, said Rothwell, are critically important to him personally and to Sanofi-Aventis as a company. ‘The problem, of course, is a healthcare system that, for many – particularly those who get bounced around within it – is fragmented and sometimes even frightening,’ Rothwell observed. ‘For those who have family members or friends who have experienced repeated encounters with the healthcare system, the only consistent thing they believe it delivers is confusion and, sometimes, flawed outcomes.’

Patient compliance automation

30x faster than PEOPLE

If you want to learn more about how to integrate your connected medical device, or if you are interested in helping with the project, give us a buzz and ask Batya or Danny for a demo.

Thanks for reading!

The role of your biostatistician for success in medical device clinical trials

medical device clinical trials

The importance of biostatistics in medical device clinical trials

In order to understand the importance of biostatistics in medical device clinical trials we talked to Dr. Lisa Deutsch.

Lisa Deutsch, Ph.D is a Managing Partner at BioStats Statistical Consulting Ltd. Lisa is one of the rare breed of biostatisticians that are specialized practitioners in biostatistics as consultants to sponsors in medical device clinical trials.

Starting off as a maths student with hopes of becoming an actuary one day, Lisa soon found out that statistics are much more interesting for her and moved into that field and as she says herself “stayed there forever”.

Her natural tendency towards all things scientific, especially in the medical field combined with the efforts of Master’s and Ph.D. supervisors (Linda Har-Nevo and Laurence Freedman respectively) effectively synthesized Lisa’s 2 passions- mathematics and biology, making her an exceptional professional in the unique space of statistical analysis planning and execution for clinical trials.

Lisa tells that while she was still at University, people started looking for consultancy and sought her advice, then got her first big time consultancy job from which eventually pulled into clinical trials and  consulting to Israeli medical device manufacturers in the are of applications for FDA approval.

The uniqueness of a medical device requires a rigorous scientific approach

Each medical device is unique in almost respects from perspective of intended use, engineering, data model, efficacy and safety.   Lisa started working in medical statistics and had to learn how to answer questions on her own and she developed her own skill-set.  That involved meticulous attention to details and thorough checking and developing a rigorous scientific approach to evaluating efficacy and safety of medical devices in clinical trials.

Trends in society drive innovative medical devices

According to Lisa, we are seeing rapid innovations and achievements in medical devices particularly in automated diagnosis and robotic procedures which are very hot fields.

People are trying to automate medicine using software as medical devices to enable quick and accurate diagnostics, to facilitate treatment, and to monitor the patients’ progress and improve clinical outcomes.

Other drivers of medical device innovations in Israel are connected with limited resources in terms of clinics and health care personnel and an aging population which create a booming market for medical device clinical trials in Israel.

As the population gets older, more people retire and the medical profession is no exception. Following the collapse of the Soviet Union, Israel experienced a huge influx of nurses and physicians. In about 20 years’ time, many of them will head towards retirement: this combined with aging population puts a great deal of pressure on Israeli healthcare.

Scientific testing in medical device clinical trials

As a result of an economy that does not have the economic resources of the US – Israeli medical device innovation is increasing turning towards automation – automation of patient adherence, automation of medical diagnosis and automation of patient monitoring.    All of this medical innovation needs to be tested scientifically in clinical trials.

The role of the biostatistician in medical device clinical trials

The role of the biostatistician in medtech clinical trials starts before the first patient enters the study with a SAP – a statistical analysis plan.  The SAP describes the planned analysis for a series of clinical trials and relates to the primary endpoints of the medical device trials, the safety endpoints and do that based on the medical device trial clinical protocol.   A SAP requires statistical expertise and abstract thinking skills.  During the medical device clinical trial, the biostatistician will be called upon to perform an interim analysis and at the end of the study a final statistical analysis to assess the efficacy and safety of the medical device.

Strong patient adherence in real life starts with strong people management


Patient adherence in real-life starts in clinical trials determining the safety, side effects and efficacy of the intervention, whether a drug or a medical device.

Like any other industry – success in clinical trials is all about the people.

The hugely successful movie – “Hidden figures” tells the story of the gifted black women mathematicians who played key roles in the NASA space program in the Mercury and Apollo space programs. It is a moving, inspiring and (sometimes hilarious) story of how NASA, a dominantly white male organization came to accept diversity during American desegregation.

By comparison, the Israeli life science industry lives in a different time and place and women are in leadership roles at all levels  of Israeli life science companies.

In this 4 part series of articles, we will tell the story of the gifted Israeli women who are the   “Hidden figures” of the Israel biomed/biotech industry.

Women comprise about 65 percent of Israel’s biotechnology workforce, and about 13 percent of top management positions in companies listed on the Tel Aviv Biomed index. In order to find out what attracts Israeli women into this globally male dominated field, I talked to a number of well-respected women, tried to learn about their story, get acquainted with their mindsets and solve the “mystery” of Israeli women invading this field.

Part 1 of the series tells the story of Hagit Nof – former Country Manager of IQVia in Israel and  currently the COO & BD of nRollmed an Israeli startup that helps clinical trial sponsors speed up their study using online patient recruitment and optimization.

(IQVia is the world’s largest provider of biopharmaceutical development and commercial outsourcing services ).

Hagit has a great story of a dream come true for a person who was not afraid to make a risky decision at the right time and was able to build a career in the biopharmaceutical industry literally from scratch.


What real-time data and Risk-based monitoring mean for your CRO

A widely neglected factor in cost-effective risk-based clinical trial monitoring is availability and accessibility of data.

RBM methods used by a central clinical trial  monitoring operation that receives stale data (any data from patients that is more than a day old is stale) are ineffective. Every day that goes by without having updated data from patients, devices and investigators reduces the relevance and efficacy of remote monitoring.

Real-time data is a sine-que-non for RBM.

Sponsors and Contract research organizations (CROs) should therefore approach real-time data and risk-based monitoring (RBM) as 2 closely related priorities for executing clinical trials. Use of modern data technologies for real-time data collection and remote risk-based monitoring will reduce non-value added rework, people and paper in clinical trials and help speed up time to statistical report.


The 3 tenets for designing a clinical data management system

This post reviews the importance of 1) proper study design, 2) good data modeling and 3) realistic estimation of project timetables. The article concludes with a discussion of eSource and attempts to dispel some of the myths including how DIY EDC study build save time (they don’t).


The trend of DIY: good for EDC vendors, less good for sponsors

The trend for small studies/IIS (investigator-initiated studies) is to use cloud EDC applications
that enable end-users to build eCRF and edit checks using a graphical user interface. This so-called DIY (do-it-yourself) approach is used by most cloud EDC vendors such as Medrio and Clincapture as a way of lowering their barriers to entry to the market.

However – what is good for vendors (lowered barriers to entry) is not necessarily good for sponsors (faster time to market of their innovative drug or medical device).


Medical device clinical trials – not for the faint of heart

Patients in medical device clinical trials are on their phones.  On their phones for WhatsApp and for monitoring chronic conditions and reporting outcomes at home, at work and in the middle of a call to their friends.

Medtech developers are looking to make their product development process as effective as  possible and are facing conflicting requirements when it comes to meeting regulatory requirements and reimbursement opportunities.


Millennials are the future of clinical trial data management

esource tp get smart to market

Millennials, born between 1980 and 2000 and the first native generation of the digital age, are the quickly approaching additions to the modern workforce. Regardless of whether private or public sector Millennials are soon to become the bulk of the global workforce.

At present, Millennials represent 34% of the current US workforce (up 9% from 25% in 2015), and by 2020 50% of workers will be of the Millennial generation. As the demographics of present job seekers continues to shift, companies need to adjust their culture, facilities and technology to cater to the new generation.

Regarding the clinical trial industry, Millennials are not only the next generation of data managers and monitors, but will soon make up the bulk of the study subjects as well.

Choosing the right tool and UX for millennial subjects becomes acute considering usability factors and patient compliance issues for people under 30.


Risk based monitoring. It’s about the people.

esource for people in clinical trials

It will come as no surprise to anyone who is actively involved in clinical trial operations that the heart of the matter in clinical trial monitoring is people.

I have written herehere and here about how people are the key assets and vulnerabilities in medical device clinical trials.

Understanding people and providing timely and high-quality communications rests is a key to data-driven decision making. There may be high value in the analysis of the data (for example – inconsistencies in dosing at sites) but if the data is not communicated in a timely and effective manner, risk based monitoring will not be effective or timely either!

MANA RBM risk based monitoring is a consultancy based in Denver CO, led by Penelope Manasco MD, that provides CRO and consulting services around risk-based monitoring. Dr. Manasco recently published an article  It Takes a Village to Achieve Risk-Based Monitoring that discusses the “people” components needed to successfully adopt Risk Based Monitoring. It also compares the roles of the Site Monitor and Central Monitor and discusses the role of risk assessment, training, and implementing Risk-Based monitoring solutions.

Good job!

There are sites who are outstanding, entering high quality data within 24 hours of the patient visit and then there are sites who take 2-3 weeks to enter data, enter future events and are not always careful regarding informed consent and participation in the trial.

This is a people issue not a technology issue.

Jenya Konikov-Rozenman is product lead at Jenya has a masters degree in biotechnology from the Hebrew University and is a doctoral candidate at Tel Aviv in medical science. She is GCP and CRA certified and leads with super-human devotion to customer delivery.

Important EDC features for medical device clinical trials

esource tp get smart to market

Medidata Rave and its CTMS companion product iMedidata are a far more comprehensive solution than OpenClinica but when you choose EDC software for medical device clinical trials, you enter a realm of unique requirements involving connectivity, security, privacy, API integration and specific interfaces to hardware.

Electronic data capture software (EDC software) systems have demonstrated that their value is manifest for clinical trial efficiency and cost savings. Soon, medical device clinical trials will no longer be dependent upon paper-based systems at all. Paper is great for passing notes in class, but how often does that even happen anymore? Kids in school are more likely to use Snapchat or simply text each other.

As someone said recently – “millenials are off Facebook, adults still use email”.